Division of Cardiology

Minimizing Heart Attack Damage

Nikolaos Frangogiannis, M.D., Professor of medicine (cardiology) A cut to the skin is usually benign: a clot forms, and maybe a small scar, but most evidence of the wound soon vanishes. Unfortunately, this minor, everyday miracle of repair and regeneration doesn’t extend to the heart. After a heart attack, the body can do little to rejuvenate damaged heart muscle. Scars form but never disappear, limiting heart function. Over time, the heart begins to change its architecture in an attempt to wring more pumping power from the weakened organ. This process, known as remodeling, may help in the short term but ultimately can lead to a host of health issues—most notably heart failure.

So the cardiologist’s first task when treating a heart attack patient is to minimize heart muscle damage, and job number two is to limit remodeling. Over the years, doctors have made great strides in achieving the former but not the latter, says Nikolaos G. Frangogiannis, M.D., professor of medicine (cardiology) and the Edmond J. Safra/Republic National Bank of New York Chair in Cardiovascular Medicine.

The problem, Dr. Frangogiannis explains, is that remodeling can take two different forms: dilated remodeling (in which the heart muscle stretches and thins) or hypertrophic remodeling (in which the walls of the heart’s ventricles thicken and stiffen). Each form requires a different treatment approach, but it’s impossible to know which disease path the heart will follow before harmful changes occur. And once remodeling starts, it’s hard to stop or reverse.

“We end up treating all heart attack patients pretty much the same way,” says Dr. Frangogiannis, who studies the molecular signals that orchestrate cardiac healing after a heart attack. “Ideally, we would have a panel of biomarkers that, together with a patient’s genetic background, clinical history and other factors, could tell us early on whether to treat for dilated or hypertrophic remodeling.”

Dr. Frangogiannis may have identified one such biomarker. In a series of studies published in Circulation, Circulation Research and the Journal of Molecular and Cellular Cardiology, he found that transforming growth factor beta (TGF-beta), a molecule involved in regulating immune and inflammatory responses as well as in tissue repair, is elevated after a heart attack and increases heart muscle stiffness. His findings suggest that TGF-beta causes connective tissue cells called fibroblasts to pump out excess collagen, which in turn leads to fibrosis and to thickening and stiffening of the heart muscle.

Dr. Frangogiannis hopes that a test will be developed (an imaging test or one that relies on genetic profiling, for example) to identify patients who have high levels of TGF-beta after a heart attack and are therefore at risk for hypertrophic remodeling. Such a test could lead to personalized post–heart attack treatment strategies that would curb the expression of TGF-beta as the heart heals.